December 04，2024，the New Drug Application (NDA) for the combination of TYVYT® (sintilimab injection) and ELUNATE® (fruquintinib) has been granted conditional approval in China for the treatment of patients with advanced endometrial cancer with Mismatch Repair proficient (pMMR) tumors that have failed prior systemic therapy and are not candidates for curative surgery or radiation. This approval follows the priority review status and breakthrough therapy designation by the National Medical Products Administration (NMPA) of China and marks the eighth approved indication for TYVYT® (sintilimab injection).
The conditional approval by the NMPA was supported by registration stage data from FRUSICA-1, the endometrial cancer registration cohort of a multi-center, open-label Phase 2 study investigating sintilimab in combination with fruquintinib in endometrial cancer patients who have experienced disease recurrence, disease progression or intolerable toxicity with treatment on platinum-based doublet chemotherapy. Results from FRUSICA-1 were presented at the American Society of Clinical Oncology annual meeting in June 2024.
A total of 98 pts with pMMR status were enrolled and received the combination treatment. All pts had previously received at least first-line platinum-containing systemic therapy, and 22.4% pts had received bevacizumab therapy. Detailed disease histories are summarized in the table. With the median (95% CI) follow-up time of 15.7m (14.6, 17.7), 87/98 pts had at least one post-baseline tumor assessment result (efficacy evaluable pts), among them, IRC-assessed ORR and DCR was 35.6% (CR: 2/87 and PR: 29/87) and 88.5% respectively; DoR was not reached and the 9m-DoR rate was 80.7%. Among 98 pts, the median (95% CI) PFS and OS was 9.5m (5.6, -) and 21.3m (17.3, -) respectively. Based on prior bevacizumab therapy, ORR was 40.9% vs 30.3%, and median (95%CI) PFS was 13.8m (4.1, -) vs 9.5m (5.5, -).
Adverse events are consistent with those reported for similar immunotherapy and antiangiogenic agents combination treatments.
About Sintilimab
Sintilimab, marketed as TYVYT (sintilimab injection) in China, is a PD-1 immunoglobulin G4 monoclonal antibody co-developed by Innovent and Eli Lilly and Company. Sintilimab is a type of immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1 / PD-Ligand 1 (PD-L1) pathway, and reactivates T-cells to kill cancer cells.In China, sintilimab has been approved and included in the updated NRDL for seven indications. The updated NRDL reimbursement scope for TYVYT(sintilimab injection) includes:
For the treatment of relapsed or refractory classic Hodgkin’s lymphoma after two lines or later of systemic chemotherapy;
For the first-line treatment of unresectable locally advanced or metastatic non-squamous non-small cell lung cancer lacking EGFR or ALK driver gene mutations;
For the treatment of patients with EGFR-mutated locally advanced or metastatic non-squamous non-small cell lung cancer who progressed after EGFR-TKI therapy;
For the first-line treatment of unresectable locally advanced or metastatic squamous non-small cell lung cancer;
For the first-line treatment of unresectable or metastatic hepatocellular carcinoma with no prior systematic treatment;
For the first-line treatment of unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma;
For the first-line treatment of unresectable locally advanced, recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma.
Furthermore, sintilimab’s eighth indication, in combination with fruquintinib for the treatment of patients with advanced endometrial cancer with pMMR tumors that have failed prior systemic therapy and are not candidates for curative surgery or radiation, was approved by the NMPA in December 2024.
In addition, two clinical studies of sintilimab have met their primary endpoints:
Phase 2 study of sintilimab monotherapy as second-line treatment of esophageal squamous cell carcinoma;
Phase 3 study of sintilimab monotherapy as second-line treatment for squamous non-small cell lung cancer with disease progression following platinum-based chemotherapy.
About Fruquintinib
Fruquintinib is a selective oral inhibitor of all three vascular endothelial growth factor (“VEGF”) receptors (VEGFR-1, -2 and -3). VEGFR inhibitors play a pivotal role in inhibiting tumor angiogenesis. Fruquintinib was designed to have enhanced selectivity that limits off-target kinase activity, allowing for drug exposure that achieves sustained target inhibition and flexibility for potential use as part of a combination therapy.
Fruquintinib is approved for marketing for the treatment of patients with metastatic colorectal cancer who have previously received fluoropyrimidine, oxaliplatin and irinotecan-based chemotherapy, and those who have previously received or are not suitable for receiving anti-VEGF therapy or anti-epidermal growth factor receptor (“EGFR”) therapy (RAS wild-type) in China, where it is co-developed and co-marketed by HUTCHMED and Eli Lilly and Company under the brand name ELUNATE. It was included in the China National Reimbursement Drug List (“NRDL”) in January 2020. Since its launch in China, over 100,000 patients with colorectal cancer have been treated with fruquintinib.
In December 2024, fruquintinib was approved by NMPA in combination with sintilimab for the treatment of patients with advanced endometrial cancer with pMMR tumors that have failed prior systemic therapy and are not candidates for curative surgery or radiation.
At present, there are still many clinical trials of new anti-cancer technologies in China seeking patients. Consultation on new drugs and technologies, you can contact Beijing South Region Oncology Hospital International Department.
Phone Number：4008803716
Email：myimmnet@163.com
References
1.https://www.nmpa.gov.cn/zwfw/sdxx/sdxxyp/yppjfb/20241203153537120.html
2.https://cn.innoventbio.com/#/news/592
3.https://meetings.asco.org/abstracts-presentations/234546
4.https://ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.5619
5.https://ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.5619
Post time: Dec-16-2024